Figure 6. GLS1-mediated reduction of oxidative stress is associated with increased phospholipid synthesis and the activation of folate and methionine cycles.

A. Differential expression of mRNA levels from genes significantly different involved either in glutathione (GSH) synthesis through the transsulfuration pathway, and the folates and methionine cycles in mice on a 0.1% MCDD and with Gls1 silencing (siGls1) versus control silencing (siCtrl) for four weeks. (Bhmt = betaine-homocysteine S-methyltransferase; Cbs = cysthationine-beta synthase; Cth = cysthathionine gamma-lyase; Gclc = glutamate-cysteine ligase, catalytic subunit; Gclm = glutamate-cysteine ligase, modifier subunit; Gls1 = glutaminase 1; GNMT = glycine N-methyltransferase; GSS = glutathione synthetase; Mat1a = methionine adenosyltransferase 1A; Mat2a = methionine adenosyltransferase 2A; Mat2b = methionine adenosyltransferase 2B; Ms = methionine synthetase; Mthfr = methylenetetrahydrofolate reductase; Mthfs = synthetase; Sahh = S-adenosyl-homocysteinase). (DMG = dimethyglycine; MTHF = L-methylfolate; SAMe = S-adenosylmethionine; SAH = S-adenosylhomocysteine; THF = tetrahydrofolate). B. Differential expression of mRNA levels from genes significantly different involved in phospholipid biosynthesis in mice on a 0.1%MCDD with siGls1 versus siCtrl for four weeks. (Cept1 = choline/ethanolamine phosphotransferase 1; Chk = choline kinase; Chpt1 = choline phosphotransferase 1; Etnk2 = ethanolamine kinase 2; Pcyt1a = phosphate cytidylyltransferase 1, choline; Pcyt2 = phosphate cytidylyltransferase 2, ethanolamine; Pemt = phosphatidylethanolamine methyltransferase; Pisd = phosphatidylserine decarboxylase; Ptdss1 = phosphatidylserine synthase 1; Ptdss2 = phosphatidylserine synthase 2). At least n=5 were used for each experimental group. Student’s t-test was used to compare the two groups and significance was set to p<0.05 (See also Supplemental Table 3).